tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist Danuglipron for Glycemic Control Among Patients With Type 2 Diabetes
Authors: Aditi R. Saxena, Juan P. Frias, Lisa S. Brown, Donal N. Gorman, Szilard Vasas, Nikolaos Tsamandouras, Morris J. Birnbaum
Journal: JAMA Network Open (2023)

Currently available glucagon-like peptide 1 receptor (GLP-1R) agonists for treating type 2 diabetes (T2D) are peptide agonists that require subcutaneous administration or strict fasting requirements before and after oral administration.To investigate the efficacy, safety, and tolerability of multiple dose levels of the novel, oral, small molecule GLP-1R agonist danuglipron over 16 weeks.A phase 2b, double-blind, placebo-controlled, parallel-group, 6-group randomized clinical trial with 16-week double-blind treatment period and 4-week follow-up was conducted from July 7, 2020, to July 7, 2021. Adults with T2D inadequately controlled by diet and exercise, with or without metformin treatment, were enrolled from 97 clinical research sites in 8 countries or regions.Participants received placebo or danuglipron, 2.5, 10, 40, 80, or 120 mg, all orally administered twice daily with food for 16 weeks. Weekly dose escalation steps were incorporated to achieve danuglipron doses of 40 mg or more twice daily.Change from baseline in glycated hemoglobin (HbA1c, primary end point), fasting plasma glucose (FPG), and body weight were assessed at week 16. Safety was monitored throughout the study period, including a 4-week follow-up period.Of 411 participants randomized and treated (mean [SD] age, 58.6 [9.3] years; 209 [51%] male), 316 (77%) completed treatment. For all danuglipron doses, HbA1c and FPG were statistically significantly reduced at week 16 vs placebo, with HbA1c reductions up to a least squares mean difference vs placebo of -1.16% (90% CI, -1.47% to -0.86%) for the 120-mg twice daily group and FPG reductions up to a least squares mean difference vs placebo of -33.24 mg/dL (90% CI, -45.63 to -20.84 mg/dL). Body weight was statistically significantly reduced at week 16 compared with placebo in the 80-mg twice daily and 120-mg twice daily groups only, with a least squares mean difference vs placebo of -2.04 kg (90% CI, -3.01 to -1.07 kg) for the 80-mg twice daily group and -4.17 kg (90% CI, -5.15 to -3.18 kg) for the 120-mg twice daily group. The most commonly reported adverse events were nausea, diarrhea, and vomiting.In adults with T2D, danuglipron reduced HbA1c, FPG, and body weight at week 16 compared with placebo, with a tolerability profile consistent with the mechanism of action.ClinicalTrials.gov Identifier: NCT03985293.
Errors in Commentary
Journal: JAMA Network Open (2023)

Physician Workforce and Its Association With Population Life Expectancy and Mortality Rates in the US" by Snyder et al. 2The commentary indicated that the total number of counties studied was 1168; it should have been given as 1618.The commentary stated that "no significant associations were found between the total proportion of PCPs and population outcomes for Black communities."It should have read "no significant associations were found between the total proportion of PCPs and life expectancy of Black populations or mortality rates among Black populations, although there was a small decrease in the Black-White mortality disparity rate."In addition, the commentary stated that "more than 50% of US counties were ineligible for this study" when it is more accurate to say that "more than 50% of US counties were ineligible at each of the 3 study time points."This article has been corrected.
Impact of dapagliflozin on cardiac remodelling in patients with chronic heart failure: The <scp>DAPA‐MODA</scp> study
Authors: Domingo A. Pascual‐Figal, J. Luis Zamorano, Mar Domingo, Herminio Morillas, Julio Nuñez, Marta Cobo Marcos, Alejandro Riquelme‐Pérez, Albert Teis, Enrique Santas, Cesar Caro‐Martinez, Jose Manuel Pinilla, Jose F. Rodriguez‐Palomares, David Dobarro, M. Alejandra Restrepo‐Córdoba, J. Ramón González‐Juanatey, Antoni Bayés Genís
Journal: European Journal of Heart Failure (2023)

ABSTRACT Aims Dapagliflozin improves the prognosis of patients with heart failure (HF), regardless of left ventricular ejection fraction (LVEF). However, its effect on cardiac remodelling parameters, specifically left atrial (LA) remodelling, is not well established. Methods and results The DAPA‐MODA trial (NCT04707352) is a multicentre, single‐arm, open‐label, prospective and interventional study that aimed to evaluate the effect of dapagliflozin on cardiac remodelling parameters over 6 months. Patients with stable chronic HF receiving optimized guideline‐directed therapy, except for any sodium–glucose cotransporter 2 inhibitor, were included. Echocardiography was performed at baseline, 30 and 180 days, and analysed by a central core‐lab in a blinded manner to both patient and time. The primary endpoint was the change in maximal LA volume index (LAVI). A total of 162 patients (64.2% men, 70.5 ± 10.6 years, 52% LVEF &gt;40%) were included in the study. At baseline, LA dilatation was observed (LAVI 48.1 ± 22.6 ml/m 2 ) and LA parameters were similar between LVEF‐based phenotypes (≤40% vs. &gt;40%). LAVI showed a significant reduction at 180 days (−6.6% [95% confidence interval −11.1, −1.8], p = 0.008), primarily due to a decrease in reservoir volume (−13.8% [95% confidence interval −22.5, −4], p = 0.007). Left ventricular geometry improved with significant reductions in left ventricular mass index (−13.9% [95% confidence interval −18.7, −8.7], p &lt; 0.001), end‐diastolic volume (−8.0% [95% confidence interval −11.6, −4.2], p &lt; 0.001) and end‐systolic volume (−11.9% [95% confidence interval −16.7, −6.8], p &lt; 0.001) at 180 days. N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) showed a significant reduction at 180 days (−18.2% [95% confidence interval −27.1, −8.2], p &lt; 0.001), without changes in filling Doppler measures. Conclusion Dapagliflozin administration in stable out‐setting patients with chronic HF and optimized therapy results in global reverse remodelling of cardiac structure, including reductions in LA volumes and improvement in left ventricular geometry and NT‐proBNP concentrations.
Chronic Obstructive Pulmonary Disease Exacerbations and Pneumonia Hospitalizations Among New Users of Combination Maintenance Inhalers
Authors: William B. Feldman, Jerry Avorn, Aaron S. Kesselheim, Joshua J. Gagne
Journal: JAMA Internal Medicine (2023)

Importance Clinical guidelines on chronic obstructive pulmonary disease (COPD) recommend inhalers containing long-acting muscarinic antagonists (LAMAs) and long-acting β-agonists (LABAs) over inhalers containing inhaled corticosteroids (ICSs) and LABAs. However, data from randomized clinical trials comparing these combination inhalers (LAMA-LABAs vs ICS-LABAs) have been conflicting and raised concerns of generalizability. Objective To assess whether LAMA-LABA therapy is associated with reduced COPD exacerbations and pneumonia hospitalizations compared with ICS-LABA therapy in routine clinical practice. Design, Setting, and Participants This was a 1:1 propensity score–matched cohort study using Optum’s Clinformatics Data Mart, a large commercial insurance–claims database. Patients must have had a diagnosis of COPD and filled a new prescription for a combination LAMA-LABA or ICS-LABA inhaler between January 1, 2014, and December 31, 2019. Patients younger than 40 years were excluded, as were those with a prior diagnosis of asthma. The current analysis was performed from February 2021 to March 2023. Exposures Combination LAMA-LABA inhalers (aclidinium-formoterol, glycopyrronium-formoterol, glycopyrronium-indacaterol, tiotropium-olodaterol, or umeclidinium-vilanterol) and combination ICS-LABA inhalers (budesonide-formoterol, fluticasone-salmeterol, fluticasone-vilanterol, or mometasone-formoterol). Main Outcome The primary effectiveness outcome was first moderate or severe COPD exacerbation, and the primary safety outcome was first pneumonia hospitalization. Propensity score matching was used to control for confounding between the 2 groups. Logistic regression analysis was used to estimate propensity scores. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models stratified on matched pairs. Results Among 137 833 patients (mean [SD] age, 70.2 [9.9] years; 69 530 [50.4%] female) (107 004 new ICS-LABA users and 30 829 new LAMA-LABA users), 30 216 matched pairs were identified for the primary analysis. Compared with ICS-LABA use, LAMA-LABA use was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation (HR, 0.92; 95% CI, 0.89-0.96) and a 20% reduction in the rate of first pneumonia hospitalization (HR, 0.80; 95% CI, 0.75-0.86). These findings were robust across a range of prespecified subgroup and sensitivity analyses. Conclusion In this cohort study, LAMA-LABA therapy was associated with improved clinical outcomes compared with ICS-LABA therapy, suggesting that LAMA-LABA therapy should be preferred for patients with COPD.
Electronic nudges to increase influenza vaccination uptake among patients with heart failure: A pre‐specified analysis of the <scp>NUDGE‐FLU</scp> trial
Authors: Niklas Dyrby Johansen, Muthiah Vaduganathan, Ankeet S. Bhatt, Simin Gharib Lee, Daniel Modin, Brian L. Claggett, Erica L. Dueger, Sandrine Samson, Matthew M. Loiacono, Rebecca C. Harris, Lars Køber, Scott D. Solomon, Pradeesh Sivapalan, Jens Ulrik Stæhr Jensen, Cyril Jean‐Marie Martel, Palle Valentiner‐Branth, Tyra Grove Krause, Tor Biering‐Sørensen
Journal: European Journal of Heart Failure (2023)

Seasonal influenza vaccination is strongly recommended in patients with heart failure (HF). The NUDGE-FLU trial recently found two electronic behavioural nudging letter strategies - a letter highlighting potential cardiovascular benefits of vaccination and a repeated letter at day 14 -effective in increasing influenza vaccination in Denmark. The aims of this pre-specified analysis was to further examine vaccination patterns and effects of these behavioural nudges in patients with HF including potential off-target effects on guideline-directed medical therapy (GDMT) use.The nationwide NUDGE-FLU trial randomized 964 870 Danish citizens ≥65 years to usual care or nine different electronic nudging letter strategies. Letters were delivered through the official Danish electronic letter system. The primary endpoint was the receipt of an influenza vaccine; additional outcomes for this analysis included GDMT use. In this analysis, we also assessed influenza vaccination rates in the overall Danish HF population including those <65 years (n = 65 075). During the 2022-2023 season, influenza vaccination uptake was 71.6% in the overall Danish HF population but this varied considerably with only 44.6% uptake in those <65 years. A total of 33 109 NUDGE-FLU participants had HF at baseline. Vaccination uptake was higher among those on higher levels of baseline GDMT (≥3 classes: 85.3% vs. ≤2 classes: 81.9%; p < 0.001). HF status did not modify the effects of the two overall successful nudging strategies on influenza vaccination uptake (cardiovascular gain-framed letter: pinteraction = 0.37; repeated letter: pinteraction = 0.55). No effect modification was observed across GDMT use levels for the repeated letter (pinteraction = 0.88), whereas a trend towards attenuated effect among those on low levels of GDMT was observed for the cardiovascular gain-framed letter (pinteraction = 0.07). The letters had no impact on longitudinal GDMT use.Approximately one in four patients with HF did not receive influenza vaccination with a pronounced implementation gap in those <65 years where less than half were vaccinated. HF status did not modify the effectiveness of cardiovascular gain-framed and repeated electronic nudging letters in increasing influenza vaccination rates. No unintended negative effects on longitudinal GDMT use were observed.ClinicalTrials.gov NCT05542004.
Outcomes Following Extracorporeal Membrane Oxygenation for Severe COVID-19 in Pregnancy or Post Partum
Authors: John J. Byrne, Amir A. Shamshirsaz, Alison G. Cahill, Mark A. Turrentine, Angela R. Seasely, Joe Eid, Caroline E. Rouse, Michael Richley, Nandini Raghuraman, Mariam Naqvi, Yasser Y. El-Sayed, Martina L. Badell, CeCe Cheng, James Liu, Emily H. Adhikari, Soha S. Patel, Erika R. O’Neil, Patrick S. Ramsey
Journal: JAMA Network Open (2023)

Importance Existing reports of pregnant patients with COVID-19 disease who require extracorporeal membrane oxygenation (ECMO) are limited, with variable outcomes noted for the maternal-fetal dyad. Objective To examine maternal and perinatal outcomes associated with ECMO used for COVID-19 with respiratory failure during pregnancy. Design, Setting, and Participants This retrospective multicenter cohort study examined pregnant and postpartum patients who required ECMO for COVID-19 respiratory failure at 25 hospitals across the US. Eligible patients included individuals who received care at one of the study sites, were diagnosed with SARS-CoV-2 infection during pregnancy or up to 6 weeks post partum by positive nucleic acid or antigen test, and for whom ECMO was initiated for respiratory failure from March 1, 2020, to October 1, 2022. Exposures ECMO in the setting of COVID-19 respiratory failure. Main outcome and measures The primary outcome was maternal mortality. Secondary outcomes included serious maternal morbidity, obstetrical outcomes, and neonatal outcomes. Outcomes were compared by timing of infection during pregnancy or post partum, timing of ECMO initiation during pregnancy or post partum, and periods of circulation of SARS-CoV-2 variants. Results From March 1, 2020, to October 1, 2022, 100 pregnant or postpartum individuals were started on ECMO (29 [29.0%] Hispanic, 25 [25.0%] non-Hispanic Black, 34 [34.0%] non-Hispanic White; mean [SD] age: 31.1 [5.5] years), including 47 (47.0%) during pregnancy, 21 (21.0%) within 24 hours post partum, and 32 (32.0%) between 24 hours and 6 weeks post partum; 79 (79.0%) had obesity, 61 (61.0%) had public or no insurance, and 67 (67.0%) did not have an immunocompromising condition. The median (IQR) ECMO run was 20 (9-49) days. There were 16 maternal deaths (16.0%; 95% CI, 8.2%-23.8%) in the study cohort, and 76 patients (76.0%; 95% CI, 58.9%-93.1%) had 1 or more serious maternal morbidity events. The largest serious maternal morbidity was venous thromboembolism and occurred in 39 patients (39.0%), which was similar across ECMO timing (40.4% pregnant [19 of 47] vs 38.1% [8 of 21] immediately postpartum vs 37.5% postpartum [12 of 32]; P &amp;amp;gt; .99). Conclusions and Relevance In this multicenter US cohort study of pregnant and postpartum patients who required ECMO for COVID-19–associated respiratory failure, most survived but experienced a high frequency of serious maternal morbidity.
Using Modern Modalities to Improve Population Health and Advance Food and Health Equity—Reply
Authors: Senbagam Virudachalam, Lydia Soo-Hyun Kim, Hilary Seligman
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Avoiding and Identifying Reversal of Left Arm and Left Leg Leads
Authors: Ding Peng, Xiulian Li, Guojun Zhao
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Evaluating Reference Ages for Selecting Prosthesis Types for Heart Valve Replacement in Korea
Authors: Sung Jun Park, You Jung Ok, Ho Jin Kim, Ye-Jee Kim, Seonok Kim, Jung-Min Ahn, Dae-Hee Kim, Jae-Sung Choi, Joon Bum Kim
Journal: JAMA Network Open (2023)

Importance Although a patient’s age may be the only objective figure that can be used as a reference indicator in selecting the type of prosthesis in heart valve surgery, different clinical guidelines use different age criteria. Objective To explore the age-associated survival-hazard functions associated with prosthesis type in aortic valve replacement (AVR) and mitral valve replacement (MVR). Design, Setting, and Participants This cohort study compared the long-term outcomes associated with mechanical and biologic prostheses in AVR and MVR according to recipient’s age using a nationwide administrative data from the Korean National Health Insurance Service. To reduce the potential treatment-selection bias between mechanical and biologic prostheses, the inverse-probability-of-treatment-weighting method was used. Participants included patients who underwent AVR or MVR in Korea between 2003 and 2018. Statistical analysis was performed between March 2022 and March 2023. Exposures AVR, MVR, or both AVR and MVR with mechanical or biologic prosthesis. Main Outcomes and Measures The primary end point was all-cause mortality after receiving prosthetic valves. The secondary end points were the valve-related events, including the incidence of reoperation, systemic thromboembolism, and major bleeding. Results Of the total of 24 347 patients (mean [SD] age, 62.5 [7.3] years; 11 947 [49.1%] men) included in this study, 11 993 received AVR, 8911 received MVR, and 3470 received both AVR and MVR simultaneously. Following AVR, bioprosthesis was associated with significantly greater risks of mortality than mechanical prosthesis in patients younger than 55 years (adjusted hazard ratio [aHR], 2.18; 95% CI, 1.32-3.63; P = .002) and in those aged 55 to 64 years (aHR, 1.29; 95% CI, 1.02-1.63; P = .04), but the risk of mortality reversed in patients aged 65 years or older (aHR, 0.77; 95% CI, 0.66-0.90; P = .001). For MVR, the risk of mortality was also greater with bioprosthesis in patients aged 55 to 69 years (aHR, 1.22; 95% CI, 1.04-1.44; P = .02), but there was no difference for patients aged 70 years or older (aHR, 1.06; 95% CI, 0.79-1.42; P = .69). The risk of reoperation was consistently higher with bioprosthesis, regardless of valve position, in all age strata (eg, MVR among patients aged 55-69 years: aHR, 7.75; 95% CI, 5.14-11.69; P &amp;amp;lt; .001); however, the risks of thromboembolism and bleeding were higher in patients aged 65 years and older after mechanical AVR (thromboembolism: aHR, 0.55; 95% CI, 0.41-0.73; P &amp;amp;lt; .001; bleeding: aHR, 0.39; 95% CI, 0.25-0.60; P &amp;amp;lt; .001), with no differences after MVR in any age strata. Conclusions and Relevance In this nationwide cohort study, the long-term survival benefit associated with mechanical prosthesis vs bioprosthesis persisted until age 65 years in AVR and age 70 years in MVR.
Prehospital Transfusion in Pediatric Trauma—The Clock Is Ticking
Authors: Robert T. Russell, Samantha M. Koenig
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Use and Costs of Instrument-Based Vision Screening for US Children Aged 12 to 36 Months
Authors: Isdin Oke, Sharon M. Lutz, David G. Hunter, Alison A. Galbraith
Journal: JAMA Pediatrics (2023)

This cohort study examines patterns and out-of-pocket costs of instrument-based screening among children 12 to 36 months.
Time to Confirmatory Study Initiation After Accelerated Approval of Cancer and Noncancer Drugs in the US
Authors: Shelley A. Jazowski, Avi U. Vaidya, Julie M. Donohue, Stacie B. Dusetzina, Rachel E. Sachs
Journal: JAMA Internal Medicine (2023)

This cross-sectional study examines and compares the time taken from the accelerated approval of cancer and noncancer drugs to the initiation of confirmatory studies in the US.
Cell metabolism-based therapy for liver fibrosis, repair, and hepatocellular carcinoma
Authors: Hélène Gilgenkrantz, Valérie Paradis, Sophie Lotersztajn
Journal: Hepatology (2023)

Progression of chronic liver injury to fibrosis, abnormal liver regeneration, and HCC is driven by a dysregulated dialog between epithelial cells and their microenvironment, in particular immune, fibroblasts, and endothelial cells. There is currently no antifibrogenic therapy, and drug treatment of HCC is limited to tyrosine kinase inhibitors and immunotherapy targeting the tumor microenvironment. Metabolic reprogramming of epithelial and nonparenchymal cells is critical at each stage of disease progression, suggesting that targeting specific metabolic pathways could constitute an interesting therapeutic approach. In this review, we discuss how modulating intrinsic metabolism of key effector liver cells might disrupt the pathogenic sequence from chronic liver injury to fibrosis/cirrhosis, regeneration, and HCC.